Nanofluidic Size-Exclusion Chromatograph

Efforts are under way to develop a nanofluidic size-exclusion chromatograph (SEC), which would be a compact, robust, lightweight instrument for separating molecules of interest according to their sizes and measuring their relative abundances in small samples. About as large as a deck of playing cards, the nanofluidic SEC would serve, in effect, as a laboratory on a chip that would perform the functions of a much larger, conventional, bench-top SEC and ancillary equipment, while consuming much less power and much smaller quantities of reagent and sample materials. Its compactness and low power demand would render it attractive for field applications in which, typically, it would be used to identify and quantitate a broad range of polar and nonpolar organic compounds in soil, ice, and water samples. Size-exclusion chromatography is a special case of high-performance liquid chromatography. In a conventional SEC, a sample plug is driven by pressure along a column packed with silica or polymer beads that contain uniform nanopores. The interstices between, and the pores in, the beads collectively constitute a size-exclusion network. Molecules follow different paths through the size-exclusion network, such that characteristic elution times can be related to sizes of molecules: basically, smaller molecules reach the downstream end of the column after the larger ones do because the smaller ones enter minor pores and stay there for a while, whereas the larger ones do not enter the pores. The volume accessible to molecules gradually diminishes as their size increases. All molecules bigger than a pore size elute together. For most substances, the elution times and sizes of molecules can be correlated directly with molecular weights. Hence, by measuring the flux of molecules arriving at the downstream end as a function of time, one can obtain a liquid mass spectrum for the molecules present in a sample over a broad range of molecular weights

Soil parameters affecting longleaf pine (Pinus palustris) site quality in east Texas

The decline since European colonization in longleaf pine (Pinus palustris Mill.) within its range in the southeastern United States, attributed to factors including both site conversion and fire exclusion has spurred interest in the re-establishment of the species. Land that originally supported longleaf pine in the southeastern United States has often been converted for agricultural use, loblolly pine (Pinus taeda Mill.) plantations, and urban development. Longleaf pine was found on a wide range of soil properties due to frequent fires which kept many competing species suppressed; fire has often been excluded due to human health, safety, and liability concerns. Longleaf pine ecosystem restoration efforts might be best focused on soils that have characteristics that naturally restrain herbaceous and hardwood competition. Properties of three soil series in east Texas that historically or are currently supporting longleaf pine ecosystems were evaluated. Analysis of Variance, Principal Component Analysis, and regression techniques were used to compare soil properties; while all three soils historically supported longleaf pine, they vary in texture, depth to argillic horizons, nutrient availability, available water capacity, and other parameters which are likely related to site quality, as measured by site index. Longleaf pine site index is influenced by depth to E and the first argillic B horizons, B horizon texture and nutrients. B horizon physical and chemical variables appear to be the most influential for longleaf pine site index on these sites, and should be considered when evaluating potential sites for longleaf pine restoration efforts

B Cell Recognition of the Conserved HIV-1 Co-Receptor Binding Site Is Altered by Endogenous Primate CD4

The surface HIV-1 exterior envelope glycoprotein, gp120, binds to CD4 on the target cell surface to induce the co-receptor binding site on gp120 as the initial step in the entry process. The binding site is comprised of a highly conserved region on the gp120 core, as well as elements of the third variable region (V3). Antibodies against the co-receptor binding site are abundantly elicited during natural infection of humans, but the mechanism of elicitation has remained undefined. In this study, we investigate the requirements for elicitation of co-receptor binding site antibodies by inoculating rabbits, monkeys and human-CD4 transgenic (huCD4) rabbits with envelope glycoprotein (Env) trimers possessing high affinity for primate CD4. A cross-species comparison of the antibody responses showed that similar HIV-1 neutralization breadth was elicited by Env trimers in monkeys relative to wild-type (WT) rabbits. In contrast, antibodies against the co-receptor site on gp120 were elicited only in monkeys and huCD4 rabbits, but not in the WT rabbits. This was supported by the detection of high-titer co-receptor antibodies in all sera from a set derived from human volunteers inoculated with recombinant gp120. These findings strongly suggest that complexes between Env and (high-affinity) primate CD4 formed in vivo are responsible for the elicitation of the co-receptor-site-directed antibodies. They also imply that the naïve B cell receptor repertoire does not recognize the gp120 co-receptor site in the absence of CD4 and illustrate that conformational stabilization, imparted by primary receptor interaction, can alter the immunogenicity of a type 1 viral membrane protein

Structure-Based Stabilization of HIV-1 gp120 Enhances Humoral Immune Responses to the Induced Co-Receptor Binding Site

The human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein, gp120, possesses conserved binding sites for interaction with the primary virus receptor, CD4, and also for the co-receptor, generally CCR5. Although gp120 is a major target for virus-specific neutralizing antibodies, the gp120 variable elements and its malleable nature contribute to evasion of effective host-neutralizing antibodies. To understand the conformational character and immunogenicity of the gp120 receptor binding sites as potential vaccine targets, we introduced structure-based modifications to stabilize gp120 core proteins (deleted of the gp120 major variable regions) into the conformation recognized by both receptors. Thermodynamic analysis of the re-engineered core with selected ligands revealed significant stabilization of the receptor-binding regions. Stabilization of the co-receptor-binding region was associated with a marked increase in on-rate of ligand binding to this site as determined by surface plasmon resonance. Rabbit immunization studies showed that the conformational stabilization of core proteins, along with increased ligand affinity, was associated with strikingly enhanced humoral immune responses against the co-receptor-binding site. These results demonstrate that structure-based approaches can be exploited to stabilize a conformational site in a large functional protein to enhance immunogenic responses specific for that region

Human resources for health policies: a critical component in health policies

In the last few years, increasing attention has been paid to the development of health policies. But side by side with the presumed benefits of policy, many analysts share the opinion that a major drawback of health policies is their failure to make room for issues of human resources. Current approaches in human resources suggest a number of weaknesses: a reactive, ad hoc attitude towards problems of human resources; dispersal of accountability within human resources management (HRM); a limited notion of personnel administration that fails to encompass all aspects of HRM; and finally the short-term perspective of HRM. There are three broad arguments for modernizing the ways in which human resources for health are managed: • the central role of the workforce in the health sector; • the various challenges thrown up by health system reforms; • the need to anticipate the effect on the health workforce (and consequently on service provision) arising from various macroscopic social trends impinging on health systems. The absence of appropriate human resources policies is responsible, in many countries, for a chronic imbalance with multifaceted effects on the health workforce: quantitative mismatch, qualitative disparity, unequal distribution and a lack of coordination between HRM actions and health policy needs. Four proposals have been put forward to modernize how the policy process is conducted in the development of human resources for health (HRH): • to move beyond the traditional approach of personnel administration to a more global concept of HRM; • to give more weight to the integrated, interdependent and systemic nature of the different components of HRM when preparing and implementing policy; • to foster a more proactive attitude among human resources (HR) policy-makers and managers; • to promote the full commitment of all professionals and sectors in all phases of the process. The development of explicit human resources policies is a crucial link in health policies and is needed both to address the imbalances of the health workforce and to foster implementation of the health services reforms

The influence of temperature fluctuation on the stability of partial nitritation applied for reject water treatment

The influence of sudden and gradual temperature fluctuations on the stability of partial nitritation applied for the treatment of reject water containing ammonium nitrogen (NH4+-N) in the range of 1000 –1400 mg/dm3 was investigated. It was found that a sudden decrease in temperature from 24.3 °C to 14.3 °C and 15.8 °C significantly affected the stability of the process. No negative effect was recorded after a sudden temperature decrease from 24.3 to 17.4 °C. It was also found that during a gradual temperature decrease from 24.3 °C, process stability was negatively affected at 12.7 °C

CHAMP gravity field recovery using the energy balance approach

International audienceSince the early days of satellite geodesy energy balance based methods for gravity field determination have been considered. If non-conservative forces are known the Hamiltonian along the orbit is a constant of the motion. Thus the gravity field can be determined if position and velocity of the satellite are known and accelerometer measurements are available to model the non-conservative part. CHAMP is the first satellite that provides the user with those three kinds of data nearly continuously. Numerical investigations using real CHAMP data are presented to show the feasibility of the method. Using a semi-analytical approach the gravity field can be determined efficiently by a 2D-Fourier method. Those fast computations also give way to application of the method not only to a full gravity field recovery but also, e.g. for quick-look and validation of SST observations for satellite missions like CHAMP, GRACE or GOCE. The method can also be used for estimation of accelerometer calibration parameters